Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen

Abstract

Amikacin requires pharmacodynamic targets of peak serum concentration (Cmax) of 8-10 times the minimal inhibitory concentration, corresponding to a target Cmax of 60-80 mg/L for the less susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30% of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient Cmax in a population of critically ill patients. Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of Cmax < 60 mg/L were identified by mixed model multivariate analysis. Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 [41-68]) were included. At inclusion, the SOFA score was 8 [6-12], 119 (66%) episodes required vasopressors, 150 (83%) mechanical ventilation, and 81 (45%) renal replacement therapy. The amikacin Cmax was 69 [54.9-84.4] mg/L. Overall, 60 (33%) episodes had a Cmax < 60 mg/L. The risk of Cmax < 60 mg/L associated with BMI < 25 kg/m(2) varied across quarters of inclusion. Independent risk factors for Cmax < 60 mg/L were a BMI < 25 kg/m(2) over the first quarter (odds ratio (OR) 15.95, 95% confidence interval (CI) [3.68-69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95% [CI 1.01-1.11], p = 0.018). Despite an amikacin dose of 25 mg/kg of total body weight, 33% of patients still had an amikacin Cmax < 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of Cmax < 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.